Early divergence of translation initiation and elongation factors

Abstract

Protein translation is a foundational attribute of all living cells. The translation function carried out by the ribosome critically depends on an assortment of protein interaction partners, collectively referred to as the translation machinery. Various studies suggest that the diversification of the translation machinery occurred prior to the last universal common ancestor, yet it is unclear whether the predecessors of the extant translation machinery factors were functionally distinct from their modern counterparts. Here we reconstructed the shared ancestral trajectory and subsequent evolution of essential translation factor GTPases, elongation factor EF-Tu (aEF-1A/eEF-1A), and initiation factor IF2 (aIF5B/eIF5B). Based upon their similar functions and structural homologies, it has been proposed that EF-Tu and IF2 emerged from an ancient common ancestor. We generated the phylogenetic tree of IF2 and EF-Tu proteins and reconstructed ancestral sequences corresponding to the deepest nodes in their shared evolutionary history, including the last common IF2 and EF-Tu ancestor. By identifying the residue and domain substitutions, as well as structural changes along the phylogenetic history, we developed an evolutionary scenario for the origins, divergence and functional refinement of EF-Tu and IF2 proteins. Our analyses suggest that the common ancestor of IF2 and EF-Tu was an IF2-like GTPase protein. Given the central importance of the translation machinery to all cellular life, its earliest evolutionary constraints and trajectories are key to characterizing the universal constraints and capabilities of cellular evolution.

Electron transport chains as a window into the earliest stages of evolution

“…Taken together, the LUCA appears to represent a population of organisms with many of the molecular systems that are seen in extant life, including protein-mediated metabolism ( 39 , 40 ), cellular organization ( 41 , 42 ), and a genetic system consisting of a DNA genome ( 43 – 45 ), RNA transcripts ( 46 ), the translation machinery ( 47 – 52 ), and the canonical genetic code ( 53 – 56 ). Given the results of proteome reconstructions and other phylogenetic analyses of ancient protein families, the LUCA appears to represent a stage in evolution well past the origin of life ( 36 ).…”

“…The branch connecting these LUCA nodes, therefore, represents an evolutionary event prior to the LUCA. Most of these universal paralog families are components of the translation system, e.g., the family containing the translation regulatory proteins Elongation Factor tu, Elongation Factor G, and Initiation Factor ( 47 ), as well as several families of aminoacyl transfer ribonucleic acid synthetases ( 48 , 49 ). Other universal paralog families encode proteins with membrane-related functions such as the SRP membrane targeting system ( 59 ), subunits of the adenosine triphosphate (ATP) synthase complex ( 60 ), and membrane-spanning ATP-binding cassette transporter (ABC-transporters) ( 58 ).…”

“…Initially, these universal paralog families were used to identify the position of the root on the tree of life ( 59 , 60 ). More recently, ancestral sequence reconstructions have been used to characterize the functions of the ancient pre-LUCA ancestral proteins ( 41 , 47 , 48 ). These reconstructions of pre-LUCA ancestral proteins all depict relatively complex, multidomain proteins that use all or nearly all of the 20 canonical biological amino acids ( 48 , 49 ).…”

Origin and Evolution of Translation: A Unifying Perspective Across Time

“…and yet remains tightly coupled to the host translation machinery and physiology [61][62][63][64][65]. Intriguingly, while the evolutionary origin of IF2 is less well known, several paths have been proposed for the diversification of elongation and initiation factors from a single ancestor at the time of LUCA [59,60,[66][67][68]. Recently, reconstruction of IF2/EF-Tu ancestry suggested that the common ancestor of IF2/EF-Tu exhibits characteristics of both IF2 and EF-Tu and evolved specialized functions after gene duplication [67].…”

Very early evolution from the perspective of microbial ecology

“…The relative simplicity of life forms at the origin compared to the relative complexity of life at the time of the LUCA suggests that many of the most foundational characteristics of life emerged during these most early stages in evolution. These include cellular organization (Harris & Goldman, 2021; Koonin, 2014), protein‐mediated metabolism (Caetano‐Anollés et al, 2009; Goldman et al, 2016), and the tripartite genetic system consisting of the DNA genome (Goldman & Landweber, 2012; Nagel & Doolittle, 1995; Poole et al, 2014), RNA transcripts (Hoeppner et al, 2012), the translation machinery (Fer et al, 2022; Fournier et al, 2011; Mushegian, 2008; Petrov et al, 2015; Woese, 1998) and the genetic code (Crick, 1968; Knight et al, 1999; Trifonov, 2000; Woese, 1965).…”